1. Field of the Invention
This invention relates to a novel orally administrable therapeutic composition having an antiplasmin inhibiting effect. More particularly, this invention relates to a novel composition comprising an anhydrous suspension of a heparinoidic factor and to the therapeutic use thereof.
2. Description of the Prior Art
Heparinoidic factors have long since come into general use as advantageous substitutes for heparin in the prophylaxis and therapy of atherosclerotic disease. In fact, though heparin is highly effective in normalizing the lipoproteinemic condition and the relation between alpha- and beta-globulins, it is well known that heparin also shows a lasting anti-coagulant action. Consequently, any prolongated treatment with this drug calls for a continuing and careful detection of the coagulation time with a view to preventing hemorrhage. It is also known that heparin cannot be satisfactorily administered either by the intramuscular route in view of the large hematoma produced at the site of the injection, or by the oral route because of instability brought about by digestive enzymes.
In the U.S. Pat. No. 3,000,787 issued to the same assignee as the present application and herein incorporated by reference, a heparinoid anti-cholesterolemic factor referred to as ATEROID was disclosed. ATEROID, which is in some aspects similar to heparin, has essentially no anti-coagulant effect at the therapeutic levels of administration per the treatment discussed hereinabove.
The aforementioned patent discloses that ATEROID can be extracted from the small intestine and particularly from the duodenum of mammals, by means of methods suitable for the isolation of aminopolysaccharidic or glycoproteic compounds. The heparinoidic factor disclosed in U.S. Pat. No. 3,000,787, for the purpose of the present specification and claims, will hereinafter be referred to as HPF-1.
Also in the U.S. Pat. No. 3,181,996 issued to the same assignee as the present application and also incorporated herein by reference, there has been disclosed a method of obtaining a heparinoidic factor of pancreatic origin. This heparinoidic factor, for the purpose of the present specification and claims, will hereinafter be referred to as HPF-2.
It is also known that plasmin is the fibrinolytic enzyme that dissolves the fibrin of blood clots obstructing normal hematic flow. An increase of plasmin inhibitors has been reported in a number of patients suffering from arterial hypertension of atherosclerotic etiology, ischemia or acute myocardial infarction, angina and cerebral thrombosis (see J. Prokopowicz et al. Thrombos. Diathesihaemorrh. 1967, 17, 1 and G. Tsitouris et al., J.Atheroscl. Res. 1967, 7, 425).
While it is known that orally administered heparin is inactive both on lipid metabolism and coagulation (see British Pat. No. 1,135,783; 1,135,784; 1,157,754; and U.S. Pat. Nos. 3,546,338 and 3,574,831), the foregoing heparin oidic factors are active on the lipid metabolism when orally administered. However, the oral administration of these factors is ineffective to decrease the level of the plasmin inhibitors. In fact, in order to decrease the level of the plasmin inhibitors by means of heparinoidic factors, it is necessary to administer them to rats by the intraperitoneal route (see Prino and Mantovani, Minerva Medica, 60, 1969, 5015-5022).
Parenteral administration of drugs is usually regarded as being undesirable because it is troublesome, time-consuming and painful to the patient. Furthermore, it requires trained personnel and carefully controlled sterile conditions at the site of administration. Consequently, it is obviously preferred to administer oral medicinal compositions, whenever the same therapeutic effect as that shown by the parenterally administered drug, can be obtained. On the other hand, the desiderability to maintain a normal antiplasmin level in patients suffering from the foregoing diseases is apparent. There is therefore an actual need for a therapeutic composition that is orally administrable to patients in need of an antiplasmin inhibiting composition.